Metrics details Plasma β-amyloid (Aβ) assays are a promising tool for Alzheimer’s disease diagnosis in clinical practice establishing an appropriate sample-handling procedure for each analytical platform is warranted This study proposes an appropriate sample-handling procedure using HISCL analyzer by elucidating the individual/combined effects of pre-analytical parameters on plasma Aβ42/Aβ40 levels We investigated the effects of various pre-analytical parameters and confirmed if these values met the acceptable criteria Plasma Aβ42/Aβ40 levels were acceptable in all conditions We determined our protocol by confirming that plasma Aβ42/Aβ40 levels remained acceptable when combining pre-analytical parameters We established an appropriate sample-handling protocol that ensures reliable measurement of plasma Aβ42/Aβ40 levels using HISCL analyzer shows promise for aiding AD diagnosis in clinical settings there is an urgent need to develop drugs that have the potential to change the progression of AD The prescribing information for lecanemab also requires confirmation of brain Aβ pathology for treatment along with the widespread administration of these promising drugs to patients there is an urgent need to establish a method to detect brain Aβ pathology in routine clinical practice Whether combined effects of these parameters on the plasma Aβ42/Aβ40 level occur is unknown protocols proposed by previous studies should be determined by evaluating the combined effects of pre-analytical parameters Schematic illustration of a sample-handling procedure from WB collection to measurement of plasma Aβ42/Aβ40 levels The following parameters were assessed: (1) storage time of WB samples at different temperatures (2) storage time of plasma samples from plasma separation to measurement (3) freezing timing after plasma separation Recovery of the plasma Aβ42/Aβ40 level in different whole blood/plasma storage conditions d) plasma storage time at RT and 4 °C on the plasma Aβ42/Aβ40 level were evaluated Plots and error bars indicate the mean values and standard deviations for 10 plasma samples The y-axis shows recovery calculated as the percentage of the Aβ42/Aβ40 level obtained in each condition compared with that obtained in the reference condition The black dashed lines show the borders of ± 10% Recovery of the plasma Aβ42/Aβ40 level in different freezing/storage conditions The effects of the (a) freezing condition and freezing timing of plasma samples stored at (b) RT or (c) 4 °C on the plasma Aβ42/Aβ40 level were evaluated Plasma samples were frozen in deep freezers at − 70 °C or − 80 °C The effects of individual pre-analytical parameters on plasma Aβ42/Aβ40 level are summarized in Table 1 We observed that plasma Aβ42/Aβ40 recovery was acceptable under all evaluated conditions To verify plasma Aβ levels in clinical practice sample-handling procedures should be determined considering the combined effects of the pre-analytical parameters This is because potential interactions between these parameters may result in unacceptable plasma Aβ levels we investigated the combined effects of these factors on plasma Aβ42/Aβ40 levels in consideration of sample handling in clinical practice we evaluated the following pre-analytical conditions: (1) WB centrifugation was performed at RT instead of 4 °C (2) plasma samples were frozen at − 20 °C in addition to below − 70 °C and (3) plasma Aβ levels were measured within 6 h at 4 °C instead of 0.5 h at RT after thawing plasma samples Combined effects of WB and plasma storage conditions on the plasma Aβ42/Aβ40 level (a) Schematic of sample handling from WB collection to measurement WB samples were stored for 2 h at RT or 6 h at 4 °C Effects of plasma storage time and temperature on the Aβ42/Aβ40 level under WB storage conditions stored for (b The condition indicated with an asterisk was analyzed using only five plasma samples because of insufficient plasma sample volumes Combined effects of WB and plasma storage and freezing conditions on the plasma Aβ42/Aβ40 level WB samples were stored for (b) 2 h at RT or (c) 6 h at 4 °C Plasma samples were frozen at − 20 °C or − 70 °C for 2 weeks after plasma storage for 2 h at RT or 6 h at 4 °C Effects of plasma storage time and temperature on the Aβ42/Aβ40 level under WB storage conditions b and c In the conditions indicated with an asterisk in (c) − 20 °C) plasma samples were excluded from the analysis because of the generation of fibrin clots with supercooling The proposed appropriate sample-handling procedure from WB collection to measurement of plasma Aβ42/Aβ40 levels Liquid nitrogen may also be used to freeze plasma samples This result is not surprising since different analytical platforms vary in sample-handling factors such as stirring speed and reaction time/temperature the effects of pre-analytical parameters on plasma Aβ42/Aβ40 levels may differ between analytical platforms establishing standard recommendations for sample handling specifically using the HISCL analyzer is important The hydrophobic property of the Aβ peptide itself may also trigger non-specific binding to hydrophobic surfaces as well as Aβ aggregation the decreased Aβ42/Aβ40 level could also be attributed to the adsorption of Aβ42 to the inner tube/tip surface by hydrophobic interaction further evaluation of Aβ peptide stability in plasma focusing on structural and molecular properties Plasma Aβ-aggregate assays (oligomer and/or fibrils) will likely help in understanding the behavior of Aβ molecules in plasma the plasma Aβ42/Aβ40 level would be used for assisting AD diagnosis with CSF and PET testing we aimed to establish acceptable plasma Aβ42/Aβ40 levels by controlling the sample-handling procedure since we developed our protocol to account for real-world application our plasma Aβ assay combined with the appropriate use of this sample-handling protocol may be feasible for implementation in routine clinical practice the % change in plasma Aβ42/40 levels may differ in subjects with AD pathology present in the brain additional studies are needed to determine the applicability of this protocol to diverse patients with different pathologies by evaluating the effects of individual and combined pre-analytical parameters on plasma Aβ levels we established a recommended sample-handling procedure for obtaining Aβ42/Aβ40 levels calculated from HISCL analyzer measurements We believe that our plasma Aβ assay coupled with our sample-handling recommendation is a promising candidate for aiding AD diagnosis in routine clinical practice Blood samples were obtained from healthy volunteers at Seishin Kenshin Center (Kobe This study was approved by the Sysmex Ethics Committee (approval number 2019–047) and conducted in accordance with the tenets of the Declaration of Helsinki All participants provided informed consent for their blood samples to be used in this study Ten blood samples from healthy volunteers were used to evaluate the effects of one pre-analytical condition on plasma Aβ levels Whole blood (WB) samples were collected in 6 mL dipotassium ethylenediaminetetraacetic acid tubes (BD Vacutainer® Blood Collection Tubes and stored at 4 °C until centrifugation (2000 g which was performed within 1 h of collection the samples were stored in polypropylene tubes (Bio-Bik and plasma Aβ40 and Aβ42 levels were measured within 30 min at RT; this was set as the reference condition The plasma samples were transferred to freezers set at − 70 °C or − 80 °C or frozen using liquid nitrogen within 30 min of plasma separation at RT Freezing timing means the time from plasma separation to freezing samples using liquid nitrogen The frozen plasma samples were thawed for 1 h at RT After evaluation of the effects of individual parameters on the plasma Aβ42/Aβ40 level the combined effects of these parameters were determined In the assessment of the combined effects of WB/plasma stability we selected the longest time from each individual pre-analytical test the following conditions were added to the evaluation of combined effects: (1) centrifugation at 2000 g for 10 min at RT and (3) storage time for 6 h after thawing the plasma samples measurements were performed after 2 weeks’ storage of plasma samples in the freezers set at − 20 °C or − 70 °C we determined whether the mean ± SD for each test was within ± 10% of the reference plasma Aβ42/Aβ40 level The data and materials obtained and/or analyzed during the study are not publicly available because of ethical concerns but are available from the corresponding author upon reasonable request Alzheimer’s disease: recent treatment strategies Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43) Amyloid imaging results from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging Alzheimer’s disease: the amyloid cascade hypothesis Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease Phase 3 trials of solanezumab and bapineuzumab for Alzheimer’s disease Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer’s disease Approval of aducanumab for Alzheimer disease-the FDA’s perspective Aducanumab: appropriate use recommendations update Lecanemab slows Alzheimer’s disease: hope and challenges Blood-based biomarkers for Alzheimer’s disease-An update Blood-based biomarkers for Alzheimer’s disease diagnosis and progression: an overview Blood-based biomarkers for Alzheimer’s disease Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation High performance plasma amyloid-β biomarkers for Alzheimer’s disease Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer disease Fully automated and highly specific plasma β-amyloid immunoassays predict β-amyloid status defined by amyloid positron emission tomography with high accuracy Preanalytical sample handling recommendations for Alzheimer’s disease plasma biomarkers Effects of pre-analytical procedures on blood biomarkers for Alzheimer’s pathophysiology Characterization of pre-analytical sample handling effects on a panel of Alzheimer’s disease-related blood-based biomarkers: results from the standardization of Alzheimer’s blood biomarkers (SABB) working group Impact of pre-analytical sample handling factors on plasma biomarkers of Alzheimer’s disease Pre-analytical variability of the Lumipulse immunoassay for plasma biomarkers of Alzheimer’s disease The scientific assessment of combined effects of risk factors: Different approaches in experimental biosciences and epidemiology The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer’s disease Confounding factors of Alzheimer’s disease plasma biomarkers and their impact on clinical performance Total Aβ42/Aβ40 ratio in plasma predicts amyloid-PET status Fully automated chemiluminescence enzyme immunoassays showing high correlation with immunoprecipitation mass spectrometry assays for β-amyloid (1–40) and (1–42) in plasma samples Download references We would like to thank all the volunteers who participated in this study All authors confirmed and substantively revised the manuscript The authors declare no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-024-65264-1 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Analytical and Bioanalytical Chemistry (2025) Sign up for the Nature Briefing newsletter — what matters in science This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Hawaii Sogetsu Branch recently celebrated its 50th anniversary with its “50 Years of Flowers” exhibit at Honolulu Museum of Art School Sogetsu Hawaii Branch began in 1964 with headmasters Sofu who nurtured its growth through exhibitions Photos by Nathalie Walker nwalker@midweek.com Privacy Policy | About Our Ads The Rotary Club of Wailuku has announced the successful acquisition of a $50,000 grant from the Rotary D5000 Foundation Maui Fires Relief Fund This grant will be used to support Piha Wellness and Healing over the upcoming fiscal year and culturally sensitive mental health providers These professionals will offer their services to individuals and families who have been impacted by the wildfires on Maui The program will be overseen by Founder and Clinical Director Michele Navarro Ishiki This funding will also enable the expedited delivery of therapeutic care bridging the gap that often exists when individuals must wait 4-6 months for mental health services By focusing on culturally sensitive approaches to mental health in the aftermath of Maui’s wildfires this initiative aims to provide individuals and families struggling with depression and other harmful behaviors with healthier coping mechanisms the goal is to help reduce trauma symptoms stemming from the devastating wildfires This initiative reflects the collaborative efforts of Rotarians to support the recovery of the Lahaina community showcasing their unity and dedication to assisting those in need KAHULUI — Four individuals packed their belongings into shopping carts on a strip of grass fronting the Shiraishi Pool on Monday when Maui County officials and police arrived shortly after 8 a.m “We don’t know where we going,” said one man before officials arrived at the Kahului pool Another man said: “I got place for go.” He said he has family and a home on Molokai “Just put as ‘Rich,’ ” he said Rich said he has been living along Kaulawahine Street for about a week and prefers to be called “houseless” rather than homeless “The cost of living is too expensive,” he said of his difficulty in finding housing Some of the people living along the sidewalk fronting the pool work He thanked people who drop off food and clothing in the area although county officials caution against it Rich and the others carted their belongings away around 10 minutes after the eviction began Rich said he’s usually the last to leave because he picks up the rubbish others leave behind “It doesn’t seem right what we are doing here (but) when you think of the entire community we got to do what we got to do,” said county Homeless Program specialist Michele Navarro Ishiki She talked to the people being evicted and picked up trash Neighbors have been concerned about homeless people congregating and camping in the area especially parents who drop off their children for swimming programs Homeless people have also gathered across the driveway to Kahului Union Church where there are senior citizen classes during the morning Most of the around 20 homeless people who linger by the fence were gone by 8 a.m Neighborhood resident Alicia Sardinha said homeless people stay up all hours of the night Some scream obscenities and threaten to kill each other “They pace up and down the street screaming It’s no longer an occasional problem but an every-night problem,” she said who has lived in the area for more than 50 years and now their children are not allowed near there without being escorted.” Sardinha has written to Mayor Alan Arakawa for help and has called police Maui County’s homeless program coordinator who said he hears her concerns about Kaulawahine Street have been working with many of these individuals for years offering assistance to get them sheltered,” Nakama wrote in a email several of those people in that area actually have housing but are choosing to hang out with their friends.” Police and county officials conduct outreach and clean areas where homeless people stay weekly and sometimes more frequently Sardinha told The Maui News that in the early ’90s she and her family started seeing homeless in their residential neighborhood and even put up gates across the driveway that stopped homeless people from approaching them but the homeless people were quiet and didn’t appear to sleep in the area the homeless people moved to Salvation Army’s banyan tree they congregated by the fence fronting the pool One man who was leaving the area Monday morning said he has been living there for five years He wanted to be identified only as “Dudoit,” and said he is originally from Waihee He pointed to places where homeless people would lay their heads such as the old swap meet property across from the Kahului McDonald’s but they moved when they realized that church sprinklers would go on at midnight Dudoit was familiar with Arakawa’s proposal to have services and possibly housing at the Old Maui High School in Hamakuapoko But “that’s a challenge,” Dudoit said noting that other needed services are in Central Maui He said he has signed up for help with the Family Life Center and is awaiting a call Ishiki said that any notice to vacate comes with offers of outreach services by the Family Life Center and community police officers She said she knows that at times people “just need a hand up.” Ishiki herself once was homeless; now some homeless people choose not to accept help from others noting the timing must be right for people to accept services people moved their carts across Kamehameha Avenue and congregated near the Kahului Shopping Center Ishiki said she recognizes that people move from one site to the next But she said the notice to vacate is a way to get homeless people to accept outreach services The last time there was a notice to vacate near the pool was Dec the county’s Public Works Department put up portable road barriers along the fence to deter camping * Melissa Tanji can be reached at mtanji@mauinews.com A grant information session for Maui County’s recycling grants program will be at 2 p.m In light of increased property values driving up tax payments the Maui County Council’s budget committee has .. Copyright © 2025 Maui News Publishing Company LTD | https://www.mauinews.com | 100 Mahalani Street By Sarah Domai Editors' Picks Jonathan Fraser’s car was found on Kuliouou Road in August 2016 Already a Honolulu Star-Advertiser subscriber? Log in now to continue reading. Jonathan Fraser was last seen July 30, 2016, at his Hawaii Kai apartment at 6233 Keokea Place, and was reported missing the following day by his family. Police found his gray 1994 Honda hatchback near the intersection of Summer Street and Kuliouou Road on Aug. 8, 2016. The FBI announced Tuesday it is offering a reward of up to $20,000 for information leading to Fraser’s whereabouts and to the arrest of the individuals responsible for his disappearance. FBI Special Agent Arnold Laanui said law enforcement has identified persons of interest but is not naming them. “We are hoping that at this point in time, the reward will be enough to uncover the leads we are looking for, so we can actually locate Mr. Fraser,” Laanui said. He said some of the leads the FBI is pursuing include individuals associated with Fraser’s vehicle and apartment. The FBI and the Honolulu Police Department previously used dogs to search for Fraser’s body based on earlier information. Fraser was involved in a fatal head-on collision in Kaneohe on Nov. 17, 2015, that killed Caleb-Jordan K. Miske-Lee. Miske’s father, Michael Miske, filed a lawsuit in November 2017, claiming that Fraser was the driver. Miske also got city approval for a controversial tree light decoration fronting Maunalua Bay during the 2017 holidays as a memorial for his son. Stay in touch with breaking news, as it happens, conveniently in your email inbox. It's FREE! Miske is suing Fraser; the driver of the other vehicle, Jared Ishiki; and Ishiki’s employer. Ishiki was driving a company vehicle at the time. The accident left Fraser with four distinctive scars on his face: one below his left eye, one under his nose and two on his chin. In a July 2016 Honolulu CrimeStoppers alert, police said Fraser suffers from a condition that requires daily medication. “The FBI will pursue these cases to its ultimate end and conclusion,” Laanui said. “And that’s ultimately bringing somebody who’s responsible to be heard in the court of law.” Individuals with information concerning the disappearance of Fraser should contact the FBI’s Honolulu Office at 566-4300. 500 Ala Moana Blvd. #2-200Honolulu, HI 96813(808) 529-4747 Parkinson’s Disease and Aging-related Movement Disorders Volume 11 - 2019 | https://doi.org/10.3389/fnagi.2019.00249 Neurodegenerative parkinsonian syndromes comprise a number of disorders that are characterized by similar clinical features but are separated on the basis of different pathologies aggregates of α-synuclein or tau protein Due to the overlap of signs and symptoms a precise differentiation is often difficult Enormous efforts have been taken to develop tau-selective PET imaging agents but strong off-target binding to monoamine oxidase B (MAO-B) has been observed across first generation ligands astrogliosis-related MAO-B elevation is a common histopathological known feature of all parkinsonian syndromes and might be itself an interesting imaging target this study aimed to investigate the performance of [18F]-THK5351 a combined MAO-B and tau tracer for differential diagnosis of parkinsonian syndromes [18F]-THK5351 PET was performed in 34 patients: six with Parkinson’s disease (PD) nine with multiple system atrophy with predominant parkinsonism (MSA-P) six with MSA with predominant cerebellar ataxia (MSA-C) and 13 with progressive supranuclear palsy (PSP) Richardson’s syndrome Volume-of-interest-based quantification of standardized-uptake-values was conducted in different parkinsonian syndrome-related target regions PET results were subjected to multinomial logistic regression to create a prediction model discriminating among groups we correlated tracer uptake with clinical findings Elevated [18F]-THK5351 uptake in midbrain and diencephalon differentiated PSP patients from PD and MSA-C MSA-C patients were distinguishable by high tracer uptake in the pons and cerebellar deep white matter when compared to PSP and PD patients whereas MSA-P patients tended to show higher tracer uptake in the lentiform nucleus A multinomial logistic regression classified 33/34 patients into the correct clinical diagnosis group and striatum was closely associated with the presence of cerebellar and parkinsonian symptoms of MSA patients The current study demonstrates that combined MAO-B and tau binding of THK5351 facilitates differential diagnosis of parkinsonian syndromes our data indicate a correlation of MSA phenotype with [18F]-THK5351 uptake in certain brain regions illustrating their relevance for the emergence of clinical symptoms and underlining the potential of THK5351 PET as a biomarker that correlates with pathological changes as well as with disease stage Especially in the early course of the disease, a precise differentiation of parkinsonian syndromes is often difficult based on clinical features alone and misdiagnosis is a frequent problem, with the most common misdiagnosis of PSP being PD and MSA (Osaki et al., 2004). This is mainly due to clinical heterogeneity and phenotypic overlap (McFarland, 2016) To this day the definite diagnosis of neurodegenerative parkinsonian syndromes still relies on post-mortem histological detection of the underlying pathology A significantly higher [18F]-THK5351 tracer retention could be detected in the midbrain and globus pallidus of PSP patients The aim of this study was to investigate the potential of combined MAO-B and tau binding of [18F]-THK5351 as a tool for differential diagnosis of neurodegenerative parkinsonian syndromes we sought to correlate individual regional tracer uptake with clinical phenotype and to compare PET results with magnetic resonance imaging Demographic and clinical data of the study sample The unified MSA rating scale (UMSARS) is the most commonly used disease-specific rating instrument in MSA and was developed to rate functional impairment independent of the underlying motor disorder (Wenning et al., 2004) To assess the amount of parkinsonian and cerebellar symptoms in our MSA cohort we calculated from the UMSARS part II a new score (UMSARS parkinsonism/cerebellar features To obtain a linear scale for correlation analysis the items facial expression tremor at rest and increased tone referring to specific parkinsonian symptoms were scaled from 0 (no impairment) to −4 (severe impairment) whereas the items ocular motor dysfunction and heel–knee–shin test referring to specific cerebellar symptoms were scaled from 0 (no impairment) to +4 (severe impairment) All other items from the UMSARS part II were not included in the generation of the UMSARS-P/C score as they measure functional impairment of complex movements and can be caused by both parkinsonian and cerebellar symptoms the UMSARS-P/C potentially ranges from −12 representing severe pure parkinsonism to +12 representing severe pure cerebellar symptoms As most MSA patients present with a combination of parkinsonian and cerebellar features the score ranged from −4 to +4 in our study cohort Automated production of [18F]-THK5351 was performed on a Raytest® SynChrom R&D single reactor synthesizer as reported previously (Brendel et al., 2017) All emission recordings were performed in a previously established protocol (Brendel et al., 2017) images were acquired using a GE Discovery 690 PET/CT scanner A prior low-dose CT scan was performed for attenuation correction Dynamic three-dimensional emission recordings were acquired during an interval of 50–70 min after intravenous injection of 183 ± 4 MBq [18F]-THK5351 The PNEURO data processing pipeline of PMOD Version 3.5 (PMOD Technologies Ltd. Switzerland) was used for spatial normalization of all [18F]-THK5351 images to the Montreal Neurological Institute (MNI) space All individual PET images were spatially normalized to the previously established [18F]-THK5351 template using the PMOD FUSION tool (equal modality; non-linear warping; 16 iterations; frequency cutoff 3; regularization 1.0; no thresholding; 8 mm transient input smoothing) Global mean intensity scaling was used for image normalization volume of interest (VOIs) were predefined in target regions known to be affected by MAO-B elevation and tau pathology in parkinsonian syndromes: midbrain Mean standard-uptake-value ratios (SUVR) relative to the global mean (SUVRGLM) were calculated for each VOI in all subjects Magnetic resonance imaging (MRI) data were available in 26/34 patients The remaining patients either refused MRI or had a contraindication to MRI In accordance with prior studies assessing morphometric MRI parameters for differential diagnosis of parkinsonism (Cosottini et al., 2007; Heim et al., 2017), we determined the ratio of the midbrain cross-sectional area scaled by the pons area. All measurements were performed in Horos open source medical image viewer1 on mid-sagittal images of T1/T2w sequences A midsagittal plane of the brain volume passing through the middle of the interpeduncular fossa and the falx cerebri was chosen (each determined on axial images) The midbrain area was determined by tracing the contour of the midbrain down to a line parallel to the hypothetic conjunction between the genu and splenium of the corpus callosum touching the superior part of the pons For the determination of the pons midsagittal area extending from the lower bound of the midbrain area down to a parallel line touching the inferior border of the pons Data were analyzed using IBM SPSS Statistics for Windows (Version 25.0. Non-dichotomized mean scores of demographic and clinical data were compared across the four groups (PD and PSP patients) via Kruskal–Wallis test and post hoc Bonferroni corrected Mann–Whitney tests Chi-square analysis was used to test for differences in gender distribution across all groups Standard statistical significance level was set at p < 0.05 For group comparisons of semiquantitative PET results in different target VOIs a Kruskal–Wallis test was performed Significance levels for the Kruskal–Wallis test were adjusted according to Bonferroni correction (p < 0.0083) Results of post hoc tests were regarded significant if they survived an additional Bonferroni correction for multiple pairwise comparisons Spearman’s test was used to explore significant correlations between PET results and clinical parameters (H&Y UMSARS-P/C) and the midbrain-to-pons area ratio calculated from MRI Four-category multinomial logistic regression was used to classify among the four disease groups using significant semiquantitative PET results as predictor variables multinomial logistic regression using MRI midbrain-to-pons area ratio as predictor was performed to compare the diagnostic utility of [18F]-THK5351 PET and MRI Demographics and clinical scores of the study sample are provided in Table 1 Patient groups did not differ significantly in terms of age Kruskal–Wallis test detected significant group differences of H&Y stage with lowest scores in PD and highest scores in PSP Significant differences of [18F]-THK5351 uptake were observed in the diencephalon, midbrain, pons, and cerebellar deep white matter (Kruskal–Wallis test, Table 2 and Figures 1A,B) [18F]-THK5351 uptake in the lentiform nucleus was highest in MSA-P patients but did not survive the significance threshold for multiple comparisons No significant differences could be detected for the striatum (A) High midbrain uptake in axial and sagittal slices allows visual discrimination of the PSP patient group from other patient groups Significantly higher [18F]-THK5351 uptake in the diencephalon was detected in PSP patients compared to PD and MSA-C patients [18F]-THK5351 uptake was especially high in the pons and cerebellar deep white matter ∗ indicates significant differences Post hoc Bonferroni tests showed that PSP patients had higher [18F]-THK5351 uptake in the diencephalon compared to PD and MSA-C and had higher [18F]-THK5351 uptake in the midbrain compared to all other patient groups whereas MSA-C patients had higher [18F]-THK5351 uptake in the pons compared to PSP and PD patients and had higher [18F]-THK5351 uptake in cerebellar deep white matter compared to PSP patients (Figures 1A,B) The multinomial logistic regression model was able to accurately classify 33/34 (97.1%) patients using the [18F]-THK5351 uptake in the diencephalon and cerebellar deep white matter as predictor variables (p < 0.05 A more conservative and therefore potentially clinically more meaningful regression model using only the [18F]-THK5351 uptake in the midbrain and pons as predictor variables was still able to correctly classify 29/34 (85.3%) patients (p < 0.05 A model using the MRI midbrain-to-pons area ratio as predictor was able to accurately classify 17/26 (65.4%) patients (p < 0.05 In order to assess the potential of [18F]-THK5351 as a biomarker of disease stage and progression a correlation analysis of tracer uptake and clinical parameters as well as with MRI atrophy was conducted We observed a significant positive correlation of H&Y stage with [18F]-THK5351 uptake in the lentiform nucleus (rs = 0.38 p = 0.01) and a negative correlation of the SEADL with [18F]-THK5351 uptake in the lentiform nucleus (rs = −0.49 There was no significant correlation of tracer uptake with disease duration Correlation of [18F]-THK5351 tracer uptake with UMSARS-P/C: (A) Correlation of [18F]-THK5351 tracer uptake in the pons (B) Axial and sagittal slices showing individual tracer uptake of patients with an UMSARS-P/C score of –4 The MRI midbrain-to-pons area ratio showed a positive correlation with [18F]-THK5351 uptake in the pons (rs = 0.49 p = 0.01) and cerebellar deep white matter (rs = 0.47 p = 0.02) and a negative correlation with tracer uptake in the diencephalon (rs = −0.54 We present the first study demonstrating the value of a combined MAO-B and tau radioligand for the differential diagnosis of neurodegenerative parkinsonian syndromes including primary tauopathies (PSP) and α-synucleinopathies (PD Tracer uptake levels of [18F]-THK5351 in the diencephalon and cerebellar deep white matter are significant predictors of clinical diagnosis our data indicate a strong association between region-specific tracer uptake and the amount of parkinsonian and cerebellar symptoms in MSA These results suggest a high amount of tracer retention being due to binding to MAO-B MAO-B was positively correlated to astrocyte proteins like vimentin MAO-B in the atypical parkinsonian syndromes MSA and PSP was significantly increased in brain areas affected by neurodegeneration This fact suggests that localized presence of α-synuclein underlies astrocytic pathology in MSA and explains the high amount of tracer uptake detected in our MSA-C patient group in these regions A multinomial logistic regression model using the midbrain-to-pons area ratio as predictor variable only led to a classification accuracy of 65.4% and was therefore worse than the model using semiquantitative PET results as predictors Our data therefore provide evidence for [18F]-THK5351 uptake in the diencephalon and cerebellar deep white matter to be of high predictive value in diagnosing the four parkinsonian syndromes under investigation Combined MAO-B and tau binding of [18F]-THK5351 seems to be of value for differentiation of parkinsonian syndromes and may be a useful diagnostic tool in the absence of 4R-tau- and α-synuclein-selective ligands In our MSA cohort tracer uptake in the striatum and cerebellar deep white matter correlated with the amount of parkinsonian and cerebellar symptoms This finding illustrates the clinical relevance of the striatum for the emergence of parkinsonian symptoms and the relevance of the pons and cerebellar deep white matter for the emergence of cerebellar symptoms in MSA and underlines the potential of [18F]-THK5351 PET as a biomarker assessing phenotype and disease stage our data disclosed a positive/negative correlation between midbrain-to-pons area ratio calculated from MRI with [18F]-THK5351 uptake in the pons and cerebellar deep white matter as well as with tracer uptake in the diencephalon and midbrain This correlation is driven by the combined effect of pontine atrophy in MSA-C patients that show a high amount of tracer uptake in the pons and cerebellar deep white matter and midbrain atrophy in PSP patients that have significantly higher tracer uptake in the diencephalon and midbrain [18F]-THK5351 retention seems to be closely related to other markers of neuronal injury This finding suggests that the presence of astrogliosis-related MAO-B elevation and tau strongly affects neurodegeneration and assures us about well-capturing neuropathological changes A limitation of the current study that needs to be considered is the absence of a neuropathological confirmation of diagnosis which reflects the moderate clinical severity within our patients the lack of a neuropathological confirmation is a general problem in studies investigating neurodegenerative disorders at an early disease stage there remains the possibility that some cases had a mismatch of clinical diagnosis and underlying pathology the present results have face validity given the agreement between [18F]-THK5351 uptake and the known topology of tau distribution in PSP patients and the topology of astrogliosis in the patient groups under investigation the tight clinical follow-up over 23.4 ± 14.1 months ensured us about the clinical diagnosis a more deep and specific cognitive assessment would have been desirable as the current study is retrospective by nature We further acknowledge the small sample size it should be noted that the current study is the first investigating [18F]-THK5351 uptake in MSA Nonetheless a larger multicenter investigation of this rare disease will be needed to evaluate the utility of [18F]-THK5351 as a combined radiotracer of tau and astrogliosis in neurodegenerative diseases Keeping these limitations in mind our findings reveal combined tau and MAO-B binding of [18F]-THK5351 to facilitate differential diagnosis of neurodegenerative parkinsonian syndromes and to correlate with phenotype and MRI atrophy [18F]-THK5351 may have limited utility as a specific biomarker of tau but may be a promising marker of neuroinflammation accompanying neurodegeneration The datasets generated for this study are available on request to the corresponding author Written informed consent was obtained by all participants in accordance with the Declaration of Helsinki Retrospective analysis of data had been approved by the Local Ethics Committee SoS and MB: research project – conception and execution; statistical analysis – design and execution; and manuscript preparation – writing of the first draft and StS: research project – execution and manuscript preparation – review and critique and MD: statistical analysis and manuscript preparation – review and critique and AD: research project – organization and manuscript preparation – review and critique AR and JL: research project – conception and organization and statistical analysis and manuscript preparation – review and critique This work was supported by the Lüneburg Foundation and the Munich Cluster of Systems Neurology (SyNergy) GH has served on the advisory boards for AbbVie UCB; has received honoraria for scientific presentations from Abbvie UCB; has received research support from CurePSP the German Academic Exchange Service (DAAD) German Parkinson’s Disease Foundation (DPG) German Research Foundation (DFG) and the German Ministry of Education and Research (BMBF) International Parkinson’s Fonds (IPF); and has received institutional support from the German Center for Neurodegenerative Diseases (DZNE) The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest MSA with predominant cerebellar ataxia; MSA-P Schwab and England Activities of Daily Living scale; SUVR UMSARS-parkinsonism/cerebellar features; VOI [18F]-THK5351 PET correlates with topology and symptom severity in progressive supranuclear palsy Progression of alpha-synuclein pathology in multiple system atrophy of the cerebellar type Assessment of midbrain atrophy in patients with progressive supranuclear palsy with routine magnetic resonance imaging Parkinson’s disease and parkinsonism: neuropathology Google Scholar Neuropathology of variants of progressive supranuclear palsy Clinical biomarkers 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tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue Diagnostic approach to atypical parkinsonian syndromes Manual MRI morphometry in Parkinsonian syndromes reduces (18)F-THK5351 uptake in the human brain a novel PET tracer for imaging tau pathology in Alzheimer’s disease Google Scholar Accuracy of clinical diagnosis of progressive supranuclear palsy Google Scholar The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy MDS clinical diagnostic criteria for Parkinson’s disease The degree of astrocyte activation in multiple system atrophy is inversely proportional to the distance to alpha-synuclein inclusions Rodriguez-Vieitez Imaging neuroinflammation: quantification of astrocytosis in a multitracer PET approach Rodriguez-Vieitez Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer’s disease Tau PET imaging: present and future directions 18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: a multicenter study Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency disorders The neuropathology of multiple system atrophy and its therapeutic implications The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS) [(18) F]AV-1451 tau positron emission tomography in progressive supranuclear palsy Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson’s syndrome a novel tau positron emission tomography imaging agent for Alzheimer’s disease Rominger A and Levin J (2019) PET Imaging of Astrogliosis and Tau Facilitates Diagnosis of Parkinsonian Syndromes Copyright © 2019 Schönecker, Brendel, Palleis, Beyer, Höglinger, Schuh, Rauchmann, Sauerbeck, Rohrer, Sonnenfeld, Furukawa, Ishiki, Okamura, Bartenstein, Dieterich, Bötzel, Danek, Rominger and Levin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Axel Rominger, YXhlbC5yb21pbmdlckBpbnNlbC5jaA==; Johannes Levin, amxldmluQG1lZC51bmktbXVlbmNoZW4uZGU=; am9oYW5uZXMubGV2aW5AbWVkLnVuaS1tdWVuY2hlbi5kZQ== †These authors have contributed equally to this work Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Aloha House Residential Treatment Program Director Michele Navarro Ishiki (from left) author Marsha Barth and Aloha House support staff member Kenui Nelson are shown at the program's Upcountry campus author and advocate Marsha Barth presented to and visited with clients at local nonprofit Aloha House’s Residential Substance Abuse Treatment Program in Makawao on Oct Novels “The Shattering: A Child’s Innocence Betrayed” and “The Shattering II: Breaking the Silence” are based on Barth’s journey of healing from childhood sexual abuse Aloha House promotes recovery and healthy lifestyles to individuals and families by providing compassionate effective and comprehensive behavioral health services with the spirit of excellence and aloha Its Residential Treatment Program serves more than 400 individuals each year Barth shared experiences from her childhood and described the process she went through to heal and move forward Clients were then able to ask questions and talk about their own struggles “We are extremely grateful to Marsha for sharing her story of hope and recovery,” said Michele Navarro Ishiki Aloha House Residential Treatment Program director woven so intricately into her painful memories A client revealed to me after the presentation that they had been abused as a child ‘She shared my story and she survived it That gives me hope that I can too’ is very powerful.” she also visited Aloha House’s partner agency Malama Family Recovery Center Maui’s only women-specific addiction treatment center “Although Marsha didn’t struggle specifically with addiction she knows the pain that our clients feel and can connect with them on a deep level Her words of inspiration showed them that they matter and provided tools they can use as they continue on their journey of recovery,” said Frances Duberstein Aloha House/Malama Development coordinator Barth’s trip also included presentations at Maui Community Correctional Center and Molokai Child Abuse Prevention Pathways in conjunction with The University of Hawaii Barnes & Noble in Kahului hosted Barth for a book-signing on Oct 13 and a portion of the proceeds from that sale will be donated to Aloha House Michele Navarro Ishiki and John Cruz at Aloha House Graduation Ceremony A total of 113 individuals were recognized during a graduation ceremony hosted by local nonprofit The graduates completed residential substance abuse treatment between June 3 Friends and family of graduates joined the festivities to honor their loved ones’ accomplishments Aloha House promotes recovery and healthy lifestyles to individuals and families by providing compassionate and comprehensive behavioral health services with the spirit of aloha Organization leaders say the Residential Treatment Program provides a structured living environment for those who need a real “time-out” from their daily lives in order to deal with their addiction issues discharge planning and assistance in developing sober support in the community The ceremony included speeches by two Aloha House alumni as well as by multiple Nā Hōkū Hanohano Award recipient and Grammy Award winner John Cruz who was born and raised in Pālolo Valley on the island of Oʻahu is open about his struggles with addiction During the event Cruz also performed a few of his songs “We were honored to have John share his message of hope with our graduates, current residents and attendees in today’s celebration,” said Michele Navarro Ishiki, Aloha House Residential Treatment Program Director “Sharing your deepest and darkest moments takes courage and it brings a sense of hope to and others that they can come back from their struggles too counselors announced each graduate by name presented them with a certificate and lei and said a few words about the journey of their client and the wishes they have for that person CJ Hoʻokano and Poi by the Pound donated food for the celebration luncheon Aloha House Residential Treatment Program Director Michele Navarro Ishiki is shown with John Cruz during the Jan Local nonprofit Aloha House held a graduation ceremony Jan 24 at Makawao Union Church’s Community Hall to celebrate and honor the 113 individuals who completed residential substance abuse treatment between June 3 and Dec Graduates’ friends and family members joined the festivities to honor their loved ones’ accomplishments The ceremony included speeches by two Aloha House alumni as well as by multiple Na Hoku Hanohano Award recipient and Grammy Award winner John Cruz who was born and raised in Oahu’s Palolo Valley Aloha House promotes recovery and healthy lifestyles to individuals and families provides a structured living environment for those who need a real “timeout” from their daily lives in order to deal with their addiction issues “We were honored to have John share his message of hope with our graduates current residents and attendees in today’s celebration,” said Michele Navarro Ishiki Aloha House residential treatment program director “Sharing your deepest and darkest moments takes courage and it brings a sense of hope to others that they can come back from their struggles too hope and also his beautiful music.” presented them with a certificate and lei and said a few words about the journey of their former client and the wishes they have for that person CJ Ho’okano and Poi by the Pound donated food for the event’s large celebration luncheon The Ron Kamonohashi: Deranged Detective anime has revealed nine additional cast members following the premiere of its first episode Diomedea is animating the series under the direction of Shota Ibata Previously announced cast members include Yohei Azakami as Ron Kamonohashi and Nao Toyama as Mofu Uzaki.Wataru Watari is doing the anime’s series composition Masakazu Ishikawa is doing the character designs Yo Tsuji is composing the music and KADOKAWA is credited for music production The theme songs include “Ikenai Fool Logic” by Unison Square Garden as the opening theme song and “Lipsync” by Hockrockb as the ending theme song describing the synopsis as:Ron Kamonohashi was once regarded as a genius at the top detective training academy he was expelled and forbidden to become a detective police officer Totomaru Isshiki knocks on Ron’s door seeking help on a serial murder case this mismatched detective team begins solving their first mystery Source: Official Website©Akira Amano Shueisha / Ron Kamonohashi: Deranged Detective Production Committee The previously announced Ron Kamonohashi: Deranged Detective anime adaptation will premiere in October of 2023 The announcement states that the “first” season is coming this fall and it also introduces the main cast Yohei Azakami and Junya Enoki will be voicing Ron Kamonohashi and Totomaru Ishiki respectively A visual featuring the two voice actors is now available: during the Jump Festa stage dedicated to the manga series a teaser visual and trailer for Ron Kamonohashi: Deranged Detective anime were revealed but without the premiere date The plot is described as:This unusual duo brings the hidden truth into the light a private investigator with serious issues team up to solve the most baffling mysteries A thrilling detective story for a new generation from Akira Amano Source: Official Twitter©Akira Amano With the Nippon Chinbotsu manga series which is about the sinking of Japan after a series of earthquakes cartoonist) Tokihiko Ishiki produced a megaseller that has remained popular until today A Manga takes this well-known example as a basis to explore the visual aesthetics and graphic-art quality of manga which have risen into a mass phenomenon of contemporary culture far beyond the isles of Japan Archive Exhibitions The company began streaming three promotional videos for its Kill Doya (Kill Self-Satisfaction) browser role-playing game on Friday The game centers on "ishiki takai-kei" (literally "high consciousness-type") words as humanoid characters The term "ishiki takai-kei" may refer to people who boast excessively with nothing to back it up people so focused on and motivated by a certain goal that they lose sight of all else or people overly concerned with their online appearances who are hyper-conscious about seeming interesting the game's anthropomorphized words may most closely relate to the first and third concepts A provided example of someone who is "ishiki takai-kei" is a Japanese person who uses English words where Japanese could be spoken and opens up their MacBook Air to work at Starbucks personified words live in an alternate world ruled by the Demon King The "ishiki takai-kei" hero Takao Isshiki suddenly appears from another world The player becomes the Demon King who strives to defeat the self-satisfied hero The Demon King and his associates strive to release the words dominated by the hero and return the world to peace The game's pre-registration period opened on Friday Depending on how many people pre-register for the game all players will receive various in-game items and characters An open beta test for the game will launch at the end of August People who participate will each receive 50 Crystals in the game A pre-registration mini game will also debut in early September DMM Games' new work will not be the first to recreate words as moe characters. IT Gijinka Keikaku (IT Anthropomorphization Project), a project that turns information technology terms into pretty girl characters, is inspiring a "Gijinka de Manabo!" (Learn via Anthropomorphization!) anime with popular voice actresses Sources: ITmedia, 4Gamer via Nijimen The Ron Kamonohashi: Deranged Detective anime has revealed the first trailer The anime is an adaptation of another manga from the author of Katekyo Hitman Reborn The new trailer features the show’s ending theme song “Lipsync” by hockrockb and it currently has 105 chapters released They describe the story:This unusual duo brings the hidden truth into the light Source: Official YouTube©Akira Amano Kadokawa debuted the second promotional video for the anime of Akira Amano's Ron Kamonohashi: Deranged Detective (Kamonohashi Ron no Kindan Suiri) manga on Sunday Jun Fukuyama as Omito Kawasemi Nao Tōyama as Mofu Uzaki Amano (Reborn!, ēlDLIVE) launched the manga on Shueisha's Shonen Jump+ website and app in October 2020 Shueisha published the manga's 11th volume on July 4 and will release the 12th volume on October 4 Amano launched the manga on Shueisha's Shonen Jump+ website and app in October 2020 Shueisha published the manga's ninth volume on January 4 Viz Media released 16 volumes of the 42-volume manga in North America and it later published the manga digitally and in print The previously announced Ron Kamonohashi: Deranged Detective anime has received a new visual as well as details on additional cast members They include Yoko Hikasa as Amamiya and Taku Yashiro as Spitz Feire Yoko Hikasa is known for her roles as Mio Akiyama in K-On! Her most recent roles include Utahime Iori in Jujutsu Kaisen Veronica de Sade in The Case Study of Vanitas and Kiyosumi Shirakawa in Call of the Night Taku Yashiro’s previous roles include Ifrit in That Time I Got Reincarnated as a Slime Tsubasa Tanuma in Kaguya-sama: Love Is War Van Reichnott in The Rising of the Shield Hero Michio Kaga in Harem in the Labyrinth of Another World and Itsuki Akasawa in The Angel Next Door Spoils Me Rotten.The main cast for Ron Kamonohashi: Deranged Detective are Junya Enoki as Totomaru Ishiki and Yohei Azakami as Ron Kamonohashi and it also announces more staff members and the October 2 premiere for the anime: The band's vocalist Ageha Horii wrote the lyrics and composed the song "Lipsync" will appear on the band's upcoming album on October 25 The "1st season" of the anime will premiere on October 2 on the AT-X. Tokyo MX The production team for the upcoming Ron Kamonohashi: Deranged Detective TV anime series will air sometime in October 2023 It is described as a “1st season,” indicating potential follow-ups in the future featuring the two main voice cast members for the anime Voice actors Yohei Azakami and Junya Enoki are playing Ron Kamonohashi and Totomaru Ishiki Azakami is photographed sitting on the left of the visual in a dark green suit while Enoki is standing on the right with a gray suit The production staff for Ron Kamonohashi: Deranged Detective includes Shota Ibata (The Saint’s Magic is Overpowered) as director Wataru Watari (The Magical Revolution of the Reincarnated Princess and the Genius Young Lady) as series screenwriter Ishikawa Masakazu (Mayoiga) as character designer and You Tsuji (The Mystic Archives of Dantalian) as music composer Diomedéa is in charge of the animation production for the series The anime is based on the mystery manga series by Akira Amano (Reborn! elDLIVE) and was first serialized in Shueisha’s Shonen Jump+ online magazine on October 11 Nine tankoubon volumes have been released as of January 2023 with a 10th volume due for release on April 4 Manga Plus releases the Ron Kamonohashi: Deranged Detective manga digitally in English and describes the story as: This unusual duo brings the hidden truth into the light Source: Ron Kamonohashi: Deranged Detective Official Twitter The Ron Kamonohashi: Deranged Detective TV anime adaptation has received its second teaser visual it was announced that Youko Hikasa and Taku Yashiro will be part of the cast a Metropolitan Police Department detective and a senior of Totomaru Ishiki a tracking instructor at the detective academy BLUE The previously announced lead voice actors are Youhei Azakami as the titular Ron Kamonohashi and Junya Enoki as Totomaru The Ron Kamonohashi: Deranged Detective manga began in October 2020 and has 11 tankoubon volumes as of July 2023 It is serialized on Shonen Jump Plus and published under Jump Comics label Shueisha’s Manga Plus service describes the plot as: The anime has the same director-series composer-character designer trio as adaptation of The Saint’s Magic Power is Omnipotent My Teen Romantic Comedy SNAFU author Wataru Watari It also shares the same animation production studio Composing the music is You Tsuji (The Mystic Archives of Dantalian) Ron Kamonohashi: Deranged Detective will premiere in October 2023 The upcoming release is described as its “1st Season.” Source: @kamonohashi_ron Shueisha announced on Sunday that Akira Amano's Ron Kamonohashi: Deranged Detective (Kamonohashi Ron no Kindan Suiri) manga will be adapted into a stage play in Tokyo and Osaka in November Yuta Kishimoto will play Ron Kamonohashi and Yutaka Nozaki will play Totomaru "Toto" Ishiki. DMM Stage is streaming comment videos from both stars: Keita Kawajiri will direct and pen the script for the show The show will run from November 1-4 at the Nippon Seinenkan Hall in Tokyo and from November 9-10 at the Sankei Hall Breeze in Osaka Amano (Reborn!, ēlDLIVE) launched the manga on Shueisha's Shonen Jump+ website and app in October 2020 Shueisha published the manga's 13th volume on March 4 The second season of the anime will premiere in October Source: Ron Kamonohashi: Deranged Detective stage play's website, Comic Natalie Kadokawa revealed a second teaser visual and more cast on Friday for the anime of Akira Amano's Ron Kamonohashi: Deranged Detective (Kamonohashi Ron no Kindan Suiri) manga The new cast includes Yōko Hikasa as Amamiya (first image below) and Taku Yashiro as Spitz Feier (second image) The "1st season" of the anime will premiere in October Kadokawa revealed nine more cast members on Friday for the anime of Akira Amano's Ron Kamonohashi: Deranged Detective (Kamonohashi Ron no Kindan Suiri) manga Amano (Reborn!, elDLIVE) launched the manga on Shueisha's Shonen Jump+ website and app in October 2020 Shueisha published the manga's 12th volume on October 4 Please enable JS and disable any ad blocker Despite some fans not expecting a comeback of the Boruto anime it seems likely that Boruto: Two Blue Vortex will be animated even though Boruto: Naruto Next Generation had divided fans’ opinions about supporting the story of Naruto’s son the Boruto: Naruto Next Generation anime seems like it just needed a break to get back on track and regain fans’ hearts as the ongoing Boruto manga has drummed up new excitement for the anime to resume The Boruto: Two Blue Vortex manga is the second chapter of the story of Boruto Uzumaki the same person behind the original Naruto manga series The first part of the Boruto: Naruto Next Generation anime ran from April 5 and now all hopes are now up to Two Blue Vortex The Two Blue Vortex manga features the highly anticipated time skip after that eventuality was hinted at in the anime The Boruto anime’s first episode featured a grown-up Boruto and Kawaki exchanging blows and swords in the devastated Village of Konoha when the Boruto: Two Blue Vortex manga was announced On August 21st, 2023, the Two Blue Vortex manga officially kicked off, exclusively available to read on Manga Plus and Viz Media. Manga Plus summarized the second chapter of the manga series as follows: “With everyone’s memories having been altered, Boruto finds himself being hunted by his own village There’s still no news on the continuation of the anime adaptation of the Boruto manga but fans can likely expect that will change as the manga continues to add new chapters it might be a while before we hear official word to ensure there’s enough manga story to avoid too many filler episodes to slow down the animated adaptation Moreover, when Two Blue Vortex gets animated, it might have seasonal launches. According to an in-depth interview with Studio Pierrot President Michiyuki Honma posted on Natalie Bleach: Thousand-Year Blood War being converted into a seasonal anime massively affected the franchise and studio as a whole positively “I think it’s great to make one long-running work like Pierrot has done in the past the large budget and running costs entail a big risk But can we compete with works made in this new way using the same production methods as before?” it is possible that the former’s success will influence how Studio Pierrot will plan the comeback of Boruto with Two Blue Vortex Hopefully a delay in the anime’s return will be for the best for the fans and the franchise Some hopeful fans have speculated its return in late 2025 or 2026 though we have no way of knowing right now Have a tip we should know? [email protected] The much-awaited anime series Ron Kamonohashi: Deranged Detective finally released its first preview trailer on August 12 exciteme­nt always reaches its pinnacle whe­n a new series is on the­ horizon With an exclusive glimpse into the world of Ron Kamonohashi: Deranged Detective anime fans can expect something extraordinary in Fall 2023 The preview trailer revealed e­ssential details including the re­lease date and staff involve­d in the project This upcoming anime se­ries has sparked considerable­ excitement within the anime community Fans eagerly anticipate­ delving into the mysterious world of Ron Kamonohashi the promotional vide­o offers a tantalizing glimpse into what lies ahe­ad for viewers of this serie­s Ron Kamonohashi: Deranged Detective is an upcoming anime­ series based on the­ manga of the same name by Akira Amano The­ highly anticipated premiere­ of this exciting adaptation is scheduled for Octobe­r 2 as unveiled in the title's first promotional video The anime­ showcases a highly talented voice­ cast. This includes Junya Enoki as Totomaru Ishiki the­ cast is expected to bring the­ characters to life and enhance the depth of the plot Ron Kamonohashi: Deranged Detective is an e­ngaging detective myste­ry manga that delves into the life­ of Ron Kamonohashi a private investigator grappling with serious issue­s they form an unlikely duo as they unrave­l perplexing mysterie­s they she­d light on hidden truths and embark on thrilling dete­ctive adventures for a ne­w generation this story promise­s excitement and intrigue­ The anime­ adaptation is currently being produced by Studio Diomedea. It is directed by Shota Ihata and feature­s a script written by Wataru Watari, along with character designs by Masakazu Ishikawa. The opening song for the anime, title­d Ikenai fool logic, will be performe­d by Unison Square Garden the rock band Hockrockb will perform the ending song The anime­ series is an adaptation of the­ manga of the same name debuted on Shue­isha's Shonen Jump+ website and app in Octobe­r 2020 As the anticipation builds for Fall 2023 e­xcitement surrounding Ron Kamonohashi: Deranged Detective re­aches its peak The re­lease date of the title has be­en revealed and a tantalizing PV offers a glimpse of what's to come Fans are now excited to delve into the­ mind of Ron Kamonohashi an extraordinary detective­ who will undoubtedly make a lasting impact on the world of anime­ by unraveling mysteries and pie­cing together clues Your perspective matters!Start the conversation By Aaheli Pradhan No Comments on Second PV of “Deranged Detective” Reveals Opening Song by UNISON Ron Kamonohashi: Deranged Detective is a promising story that includes intriguing “impossible crimes” scenarios and the unusual duo that take it upon themselves to solve these cases Deranged Detective is all set to debut early in October Here’s everything you need to know about Deranged Detective before it releases Kadokawa debuted the second promotional video for Akira Amano’s Ron Kamonohashi: Deranged Detective (Kamonohashi Ron no Kindan Suiri) The anime will premiere on October 2 on the AT-X The second promotional video of Deranged Detective features the first meeting of Ron Kamonohashi and Totomaru Ishiki Ishiki is surprised by the bareness of Ron’s room Ron explains that he is cut off from the outside world He also tells Toto he will become a great detective starting today The promotional video also features the opening song from UNISON SQUARE GARDEN titled “fool logic.” Crunchyroll will stream the anime starting October 2 under “Ron Kamonohashi’s Forbidden Deductions.” Shōta Ihata of The Saint’s Magic Power of Omnipotent fame directs the anime at diomedéa Yōhei Azakami will be playing the titular character of Ron Kamonohashi while Junya Enoki will play the role of Toto Kadokawa has also revealed more cast members along with the second promotional video Most of us grew up liking detective stories and it has something to do with our inherent curiosity We all appreciate a great detective who is kind of twisted with his dull but “good at heart” buddy get ready to join this eccentric detective duo on October 2nd Source: Kadokawa Binge-reads a massive amount of manga from psychological to shounen-ai All content cited is derived from their respective sources. 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